Antibiotic resistance is a worldwide problem (J. Med. Chem., 1996;39:3853) with catastrophic potential (Southern Med. J., 1995;88:797). In 1995, the American Society of Microbiology Task Force issued a report defining the resistance problem and calling for new antibacterial agents with novel structures or mechanisms to offer alternatives to existing therapeutic choices.
The quinolone antibacterials as exemplified by ciprofloxacin 1 represent a significant addition to the therapeutic options currently available. The quinolones are potent, inhibit gram positive and gram negative bacteria, and may be administered orally or IV. The quinolones also have several significant side effects (J. Antimicrob. Chemother., 1994;33:685), and significant resistance has been frequently noted (Gootz, Medicinal Research, 1996;Rev. 16:433). 
The quinolones have a distinct structure activity relationship which has been defined by several thousands of analogs prepared over the last 30 years (Progress in Drug Research, Editor S. Mitsuhashi, 1992;38:11-147). In the quinolone SAR, it is well-established that the N1 group with the C3-carboxyl and the C4 carbonyl are essential for activity and that any substituents at C2 detract from activity (J. Antimicrob. Chemother., 1994;33:685 and Gootz, supra., 1996). It is also well-established that R6 is ideally fluorine, and that R7 is a nitrogen containing heterocycle. R1 is ideally a small alkyl, cycloalkyl, or a phenyl group. 
The quinolones inhibit bacterial growth by inhibition of DNA gyrase and Topoisomerase IV (Gootz, supra., 1996). The gyrase interaction appears to rely on the N1xe2x80x94C4-carbonyl-C3-carboxyl relationship.
Attempts to design novel quinolone mimics have focused on the N1xe2x80x94C4-carbonyl-C3-carboxyl relationship. Compounds of type 3 were designed to keep an all planar relationship and to have the NH of the isothiazole ring be as acidic as the quinolone CO2H (Chu, Drugs Exptl. Clin. Res., 1990;16:215). While maintaining excellent quinolone activity, these compounds also showed antitumor and mammalian topoisomerase activity (Drugs of the Future, 1992;17:1101) which is undesired in an antibacterial agent. 
Several publications (U.S. Pat. No. 5,283,248; J. Med. Chem., 1992;35:1358; Antimicrob. Agents Chemother., 1995;39:163) cite compounds of type 4 as having antibacterial activity and inhibition of DNA gyrase. In compounds 4, the relationship of the N1 to the C4 carbonyl has been skewed. Compounds of type 4 were also ineffective against bacteria that were quinolone resistant. 
Compounds of type 5 have also been revealed as quinolone mimics (JP 4,091,090 March 1992; Interscience Conference on Antimicrobial Agents and Chemotherapy 1991, Abstract 1494). These agents were reported to possess antibacterial and gyrase activity. While the ideal N1xe2x80x94C4-carbonyl relationship is maintained in 5, the C2 region where substitution is undesirable in the quinolones is filled with a major part of the ring. None of the quinolone mimics 3-5 exactly mimics the quinolone parent structure because all contain an extra third ring used to deliver the acidic H group required for activity.
WO 96/04288 describes a series of benzoheterocycles 6 which are glycine receptor antagonists. X, Y, and Z are chosen to provide hydrogen bond acceptor and donator groups. Among the compounds depicted are some N-hydroxy-quinazoline-2,4-diones 7, where R1-R4 may be hydroxy, amino, nitro, a variety of alkyls, esters, and amides. In all cases, the substituent on N1 is hydrogen. None of the substituents R1-R4 are nitrogen containing heterocycles. No antibacterial activity is revealed. 
U.S. Pat. No. 5,155,110 (October 1992) reveals certain N1-aryl-N-hydroxy-quinazoline-2,4-diones 8 as cyclooxygenase and lipoxygenase inhibitors. R may be halo, cyano, hydroxy, and substituted amino. Amino heterocycles are not included in R, and no antibacterial activity is described. 
Described are compounds of Formula I which are new: 
or a pharmaceutically acceptable salt thereof wherein:
R1 is H, a straight or branched alkyl of 1 to 6 carbons, cycloalkyl of 3 to 6 carbons, a heterocycle of 4 to 6 atoms having 1 to 2 heteroatoms, or a phenyl group, each is optionally substituted by R, F, Cl, OR, or N(R)2 wherein R is H, a straight or branched alkyl of 1 to 6 atoms having 0 to 1 degrees of unsaturation, a ring of 3 to 6 atoms having 0 to 2 heteroatoms, or a phenyl group, each may be substituted by F, Cl, CN, NO2, OH, NH2; also, two R""s may form a 3- to 7-membered ring with the atom to which it is attached which ring may have 0 to 1 heteroatoms;
R5, R6, and R8 are each independently H, F, Cl, Br, NO2, CN, CF3, (C(R)2)nOR, (C(R)2)nCO2R, (C(R)2)nCON(R)2, (C(R)2)nN(R)2, (C(R)2)nNRCOR, a straight or branched alkyl of 1 to 4 carbons containing 0 to 1 degrees of unsaturation, a cycloalkyl of 3 to 6 carbons, each optionally substituted by F, Cl, OR, or N(R)2 wherein R is as defined above;
R1 and R8 may form a ring of 6 to 7 atoms having 1 to 2 heteroatoms which ring may be substituted by one or more R""s wherein R is as defined above;
R7 is selected from R5, R6, R8, a carbocycle of 3 to 7 carbons, a phenyl, or a heterocyclic ring of 4 to 7 atoms, a fused heterocyclic ring of 8 to 10 atoms, a bicyclic heterocycle of 6 to 9 atoms, or a spiro heterocycle of 7 to 12 atoms each having 1 to 4 heteroatoms, and each of which is optionally substituted by one or more of Rxe2x80x2, F, Cl, (C(R)2)nN(R)2, (C(R)2)nOR, O, (C(R)2)nCON(R)2, (C(R)2)nCOR, (C(R)2)nNRCOR, (C(R)2)nCO2R, wherein R is defined above and Rxe2x80x2 is defined as R which is defined above; any of the adjacent groups R5-R8 may together form a 5- to 7-membered ring having 0 to 2 heteroatoms, which rings may be substituted by any of the groups described for R7;
n is an integer of from 0 to 3; and
X and Y are each independently carbon or nitrogen with the understanding that if X or Y is nitrogen, no substituent R6 or R8 is attached.
The invention is also a pharmaceutical composition of the above compounds and methods of using the compounds as pharmaceuticals useful in the treatment of bacterial infection.